Venous thromboembolism is an infrequent, but important, complication of pregnancy. It complicates approximately 1 in every 1000 pregnancies, and the tragic complication of fatal pulmonary embolism complicates approximately 1 in every 100,000 deliveries.1 Pregnant women are twice as likely to develop pulmonary embolism as age-matched nonpregnant women, and the risk of pulmonary embolism increases approximately 30-fold after delivery. These facts compel clinicians to maintain vigilance for pulmonary embolism during pregnancy and postpartum and evaluate symptoms that suggest pulmonary embolism.
However, evaluation of suspected pulmonary embolism during pregnancy presents challenges. Physiologic changes of normal pregnancy can mimic symptoms and signs of venous thromboembolism. As a consequence, clinicians have a difficult time knowing when to pursue a diagnosis of pulmonary embolism. No model of testing threshold exists for pregnant women, even though clinician investigators have developed a scientific rationale to identify patients who are not pregnant for whom the likelihood of pulmonary embolism (testing threshold) is sufficiently high to warrant diagnostic testing.2 Clinical prediction rules such as the Wells Score validated for patients who are not pregnant may not accurately assess the pretest probability of pulmonary embolism during pregnancy. To compound the problem, increased D-dimer levels characterize normal pregnancies and confound the use of this simple test to exclude pulmonary embolism safely.3,4 Furthermore, radiation exposures from imaging to evaluate suspected pulmonary embolism pose increased risks for the mother and fetus. Exclusion of pregnant women from rigorous contemporary studies of protocols to diagnose pulmonary embolism means that reliable data are not available, which adds to the challenge.
With this background, an official ATS/STR clinical practice guideline is welcome. The guideline represents a consensus developed by a multidisciplinary panel using an evidence-based approach.5 Panelists integrated explicit and transparent values into their final guidelines, a departure from guidelines provided by a task force of the European Society of Cardiology (ESC).6
What are the guidelines and how should we use them? First, the ATS/STR panelists recommend that D-dimer tests not be used to exclude pulmonary embolism in pregnant women. ESC guidelines differ. The European task force asserted that normal D-dimer levels can exclude pulmonary embolism for pregnant women just as for other patients with suspected pulmonary embolism, even though normal D-dimer levels are less likely to be found late in pregnancy. The ATS/STR panelists identified a retrospective study7 and 2 case reports8,9 of negative D-dimer tests in pregnant patients diagnosed with pulmonary embolism. One case9 involved a negative SimpliRED D-dimer test (a qualitative assay of moderate sensitivity), and the other case8 involved a negative auto-dimer assay possibly confounded by concomitant anticoagulant treatment. Although far from rigorous investigations, the retrospective study and the 2 cases confirm the fact that pulmonary emboli can be found in pregnant patients with negative D-dimer tests. Neither the retrospective study nor the case reports offer compelling evidence to guide medical decisions. More rigorous investigations are needed to define what role highly sensitive enzyme-linked immunosorbent assay D-dimer tests should play when clinicians suspect pulmonary embolism in pregnant patients. Until such data become available, the guidelines proposed by the ATS/STR committee appear wise.
Both the ATS/STR and the ESC guidelines recommend lower limb compression ultrasonography because identification of deep vein thrombosis warrants treatment without further imaging. ESC guidelines advocate venous ultrasonography for all pregnant patients with suspected pulmonary embolism and a positive D-dimer test, whereas the ATS/STR guidelines recommend venous ultrasonography only for pregnant patients with symptoms or signs of deep vein thrombosis. Regardless of which approach is taken, suspected pulmonary embolism must be pursued if venous compression ultrasonography is negative.
The ATS/STR guidelines provide explicit recommendations for chest radiographs as the first radiation-associated imaging procedure, followed by a lung perfusion scan if the chest radiograph is normal and computed tomography pulmonary angiography if the chest radiograph is abnormal. The ESC guidelines are less explicit, but both ATS/STR and ESC panelists agree that (1) nondiagnostic lung scans should lead to further imaging and (2) computed tomography pulmonary angiography is preferable to conventional pulmonary angiography.
The ATS/STR panelists call attention to the low quality of available evidence. Clearly, development of high-quality evidence is the way forward. Derivation and validation of testing thresholds and clinical prediction rules for the assessment of pretest probability of pulmonary embolism for pregnant patients is needed. The use of higher cutoff points for sensitive D-dimer tests may enhance specificity while preserving the sensitivity of these tests to exclude pulmonary embolism without radiation-associated imaging in low-risk patients.3 Technical and procedural advances to ensure high-quality images while minimizing radiation exposure are needed to enhance safety when radiation-associated imaging is necessary.
In conclusion, the ATS/STR panelists have made an important contribution, not only by providing a current evidence-based clinical practice guideline but also by providing a stimulus for further research.
1. Marik PE. Venous thromboembolism in pregnancy. Clin Chest Med. 2010;31:731–740
2. Lessler AL, Isserman JA, Agarwal R, et al. Testing low-risk patients for suspected pulmonary embolism: a decision analysis. Ann Emerg Med. 2010;55:316–326, e311
3. Chan WS, Lee A, Spencer FA, et al. D-dimer testing in pregnant patients: towards determining the next “level” in the diagnosis of deep vein thrombosis. J Thromb Haemost. 2010;8:1004–1011
4. Chabloz P, Reber G, Boehlen F, et al. TAFI antigen and D-dimer levels during normal pregnancy and at delivery. Br J Haematol. 2001;115:150–152
5. Leung AN, Bull TM, Jaeschke R, et al. An official ATS/STR clinical practice guideline: evaluation of suspected pulmonary embolism in pregnancy. Am J Respir Crit Care Med
6. Torbicki A, Perrier A, Konstantinides S, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008;29:2276–2315
7. Damodaram M, Kaladindi M, Luckit J, et al. D-dimers as a screening test for venous thromboembolism in pregnancy: is it of any use? J Obstet Gynaecol. 2009;29:101–103
8. To MS, Hunt BJ, Nelson-Piercy C. A negative D-dimer does not exclude venous thromboembolism (VTE) in pregnancy. J Obstet Gynaecol. 2008;28:222–223
9. Levy MS, Spencer F, Ginsberg JS, et al. Reading between the (Guidelines). Management of submassive pulmonary embolism in the first trimester of pregnancy. Thromb Res. 2008;121:705–707